Consolidative 32P after second-look laparotomy for ovarian carcinoma.
We report our experience with consolidative 32P after second-look laparotomy. Forty-three patients received consolidative 32P after platinum-based chemotherapy and a negative (39 patients, 91%) or positive (4 patients) second-look laparotomy. Thirty-one patients (72%) initially had stage III (30 patients) or stage IV (1 patient) disease; 28 patients (65%) had grade 3 tumors. Patients had follow-up from 3.5 to 14.9 years (median, 7.7 years); no patient was lost to follow-up. The 5-year rates of control of disease within the abdomen (local control) for the overall group and the subset of patients with stage II-IV disease and a negative second-look laparotomy were 65% and 69%, respectively. The corresponding 5-year survival rates were 78 and 81%, respectively. Multivariate analyses revealed that tumor found at second-look laparotomy significantly influenced the likelihood of local control and cause-specific survival. Acute side effects included cellulitis (1 patient) and ileus (3 patients). Two patients (5%) experienced severe late complications; both experienced small bowel obstruction that necessitated surgical intervention. Consolidative 32P appears to reduce the risk of recurrence and improve survival after negative second-look laparotomy. The risk of significant complications is low.


Qualitative Perfusion Cardiac Magnetic Resonance Imaging Lacks Sensitivity in Detecting Cardiac Allograft Vasculopathy.
Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation, requiring frequent surveillance angiography. Though cardiac angiography is the gold standard, it is insensitive in detecting transplant vasculopathy and invasive. Perfusion MRI provides a noninvasive alternative and possibly a useful modality for studying CAV. We sought to compare the accuracy of qualitative perfusion MRI to coronary angiography in detecting CAV. A retrospective analysis was performed in 68 heart transplant recipients who had simultaneous surveillance cardiac MRI and coronary angiogram and who underwent transplantation between 2000 and 2007. We compared results of qualitative MRI to those of the cardiac angiogram. Sensitivity and specificity of MR were calculated. Sixty-eight patients underwent both cardiac MRI and coronary angiogram. 73.5% were male; mean age was 45.37 ± 14 years. Mean duration of heart transplantation was 7.9 ± 5.2 years. The mean ejection fraction was 55% in the patients without CAV and 57.4% in those with CAV. There were 48 normal and 24 abnormal MRI studies. The overall sensitivity was 41% and specificity was 74%. Qualitative assessment of perfusion cardiac MR has low sensitivity and moderate specificity for detecting CAV. The sensitivity of MRI was slightly improved with severity of disease.


Experience of segmentectomy from 36 Chinese patients with non-small cell lung cancer at stage I.
Although video-assisted radical operation for lung cancer has been widely accepted for treatment of nonsmall cell lung cancer (NSCLC), the debate over video-assisted thoracic surgery (VATS) segmentectomy still remains. This study analyzed the clinical outcomes using VATS segmentectomy for stage I NSCLC patients to explore the safety and efficacy of VATS segmentectomy for Ia NSCLC. Retrospective review was conducted of patients who underwent VATS segmentectomy for clinical stage I NSCLC at Shanghai Chest Hospital between November 2009 and May 2012. VATS segmentectomy was performed on 36 patients. Analyses of the patient group were performed on patient demographics and clinical characteristics, intraoperative parameters, complications, and postoperative survival. Thirty-five of thirty-six patients underwent VATS segmentectomy with only one conversion to open thoracic surgery. There was one peri-operative mortality from the segmentectomy group and all other patients are alive with a median follow up of 327 days. The mean volume of chest tube drainage after operation for segmentectomy was 1021.4 ml. Among other parameters, the mean blood loss was 162.5 ml (50.0 - 1600.0 ml), the mean operation time 124.8 minutes (75.0 - 271.0 minutes), chest tube duration 4.1 days (2 - 8 days), and the mean length of hospital stay 6.2 days (4 - 11 days). There was one (2.8%) locoregional recurrence after segmentectomy. Two patients successfully underwent bilateral segmentectomies and are still disease free. For patients with stage I NSCLC, VATS segmentectomy offers a safe and equally effective option and can be applied to complicated operations such as bilateral segmentectomy.


Effects of a dental food on plaque accumulation and gingival health in dogs.
Recent studies have demonstrated that typical dry dog foods have significantly less efficacy in reducing accumulation of dental substrates compared to a specifically formulated and processed dental food. This study compared the effects of a typical dry food and a dental food on plaque accumulation and gingival inflammation in dogs during a 6-month period. Daily feeding of the dental food significantly reduced plaque and gingivitis by 39% and 36%, respectively, compared with daily feeding of the typical dry food. Feeding a food that decreases plaque accumulation and reduces gingivitis contributes to canine oral health maintenance.


[Successful therapy of a postpartum lymphangioleiomyomatosis. Case report and literature review].
Immediately after delivery a 17-year-old Turkish primipara developed edema, supraclavicular lymphoma and pleural effusion. CT-scans showed massive abdominal and mediastinal lymphoma. Lymphangioleiomyomatosis (LAM) was diagnosed by supraclavicular and retroperitoneal biopsy and progesterone receptors were documented in the tumor. There was no evidence of pulmonary involvement. 5 months' treatment with the LHRH-analogue goserelin showed neither clinical improvement nor regression of LAM. Irradiation of the ovaries and the abdomen with 30.2 Gy was followed by amenorrhea without immediate tumor remission. A follow-up examination 1 year later revealed clinical improvement and CT scans showed 50% abdominal and mediastinal regression of LAM. 5 1/2 years after diagnosis the asymptomatic patient is still in partial remission. Successful treatment of LAM is rare. We describe a case in which a major tumour reduction was documented by CT scanning.


Clinical performance and peri-implant parameters of 132 implants supporting locator-retained overdentures: a case series of 33 patients.
The aim of this study was to assess the long-term reliability of Locator-retained mandibular or maxillary overdentures and to examine clinical and radiographic parameters of the supporting implants. The authors performed a retrospective analysis of a case series. After implant placement and a submerged healing phase of about 3 months, all implants were restored with Locator-retained overdentures. The follow-up examinations included the assessment of the Plaque Index (PI) and sulcus Bleeding Index (SBI) as well as peri-implant soft tissue parameters, such as bleeding on probing (BOP) and pocket probing depth (PPD). The mean marginal bone loss was measured on panoramic radiographs. The clinical performance of Locator components and the prosthetic restoration were evaluated. Descriptive statistics were computed. For statistical analysis, non-parametric and parametric tests with respect to the variable scale were used. The significance level was set as P ≤ .05. The sample was composed of 33 patients (18 men, 15 women) with a mean age of 66.8 years who received 132 implants (84 in the anterior maxilla, 48 in the anterior mandible). After 32.9 months of follow-up, one maxillary implant was lost. All prosthetic restorations were still functionally in place at the last follow-up appointment with moderate prosthodontic maintenance effort. Clinical parameters and radiographs revealed healthy tissues around most implants. Within the limitations of this study, it can be concluded that Locators are a predictable alternative for anchorage of mandibular and maxillary overdentures with good clinical performance of both the prosthetic restorations and the supporting implants.


PSNet: prostate segmentation on MRI based on a convolutional neural network.
Automatic segmentation of the prostate on magnetic resonance images (MRI) has many applications in prostate cancer diagnosis and therapy. We proposed a deep fully convolutional neural network (CNN) to segment the prostate automatically. Our deep CNN model is trained end-to-end in a single learning stage, which uses prostate MRI and the corresponding ground truths as inputs. The learned CNN model can be used to make an inference for pixel-wise segmentation. Experiments were performed on three data sets, which contain prostate MRI of 140 patients. The proposed CNN model of prostate segmentation (PSNet) obtained a mean Dice similarity coefficient of [Formula: see text] as compared to the manually labeled ground truth. Experimental results show that the proposed model could yield satisfactory segmentation of the prostate on MRI.


Isomeric interconversion in the linear Cl(-)-HD anion complex.
The rotationally resolved infrared photodissociation spectrum of Cl(-)-HD is measured in the HD stretch region. Two Sigma-Sigma bands are observed, corresponding to transitions from the ground state [the (nuHD = 0, n = 0) level] and first excited intermolecular bend state [the (nuHD = 0, n = 1) level]. The (nuHD = 0, n = 0) and (nuHD = 0, n = 1) states are predominantly associated with the linear Cl-...DH and Cl-...HD geometries, respectively. The spectrum is complicated by perturbative interactions between levels of the (nuHD = 0, n = 0) and (nuHD = 0, n = 1) rotational manifolds and between levels of the (nuHD = 1, n = 0) and (nuHD = 1, n = 1) rotational manifolds. A global fit to the transition frequencies, taking the lower and upper state perturbations into account, yields zero-order rotational and centrifugal distortion constants and allows us to establish that the (nuHD = 0, n = 1, J" = 0) level lies 13.7 cm(-1) above the (nuHD = 0, n = 0, J" = 0) level. Rovibrational energy level calculations performed using a recent ab initio potential energy surface confirm the picture emerging from the experimental data and provide good agreement with measured molecular parameters. The results emphasize the importance of quantum mechanical interconversion between two isomeric structures of a simple anion complex.


Demographic and developmental differences in the content and sequence of adolescents' ideal romantic relationship behaviors.
This study utilizes data from 18,392 respondents (aged 12-19) in Wave 1 of the National Longitudinal Study of Adolescent to Adult Health (Add Health) to provide a detailed descriptive analysis of U.S. adolescents' desired behaviors in their ideal romantic relationships. Age, gender, and ethnic group differences in the desire for--and preferred sequence of--a set of activities that could occur in a hypothetical romantic relationship were explored within subsets of heterosexual (n = 17,274) and sexual minority adolescents (n = 1118). Non-sexual behaviors were more commonly desired compared to sexual behaviors. The typical desired behavioral sequence was: holding hands, going out alone, telling others they were a couple, kissing, saying "I love you," sexual touching, and finally having sex. Overall, more similarities than differences emerged across groups, with some notable differences in the percentages who desired sexual behaviors. Results provide a nuanced picture of adolescent relationship scripts, with implications for education and prevention.


[Use of polyacrylate dispersions for spray coating phenobarbital. 1: Production and in vitro study of microcapsules].
The production of microcapsules (model drug: phenobarbital) using aqueous polyacrylate dispersions by means of spray drying is described. The influence of the following factors on formation and quality of the microcapsules is discussed: particle size of the drug, composition of the polyacrylate, viscosity of the spray material and quantitative relation between the drug and the coating material. The morphology of the microcapsules is investigated by means of light and screen electronic microscopy. The liberation of the drug is evaluated. Mainly dry spheric microcapsules arise in a one-working step. Their properties are influenced by variation of the polyacrylate composition. The liberation of the drug decreases with decreasing drug concentration (80-20%) and in dependence of the polyacrylate dispersion for spray coating and the resulting film.


c-Met inhibitors attenuate tumor growth of small cell hypercalcemic ovarian carcinoma (SCCOHT) populations.
A cellular model (SCCOHT-1) of the aggressive small cell hypercalcemic ovarian carcinoma demonstrated constitutive chemokine and growth factor production including HGF. A simultaneous presence of c-Met in 41% SCCOHT-1 cells suggested an autocrine growth mechanism. Expression of c-Met was also observed at low levels in the corresponding BIN-67 cell line (6.5%) and at high levels in ovarian adenocarcinoma cells (NIH:OVCAR-3 (84.4%) and SK-OV-3 (99.3%)). Immunohistochemistry of c-Met expression in SCCOHT tumors revealed a heterogeneous distribution between undetectable levels and 80%. Further characterization of SCCOHT-1 and BIN-67 cells by cell surface markers including CD90 and EpCAM demonstrated similar patterns with differences to the ovarian adenocarcinoma cells. HGF stimulation of SCCOHT-1 cells was associated with c-Met phosphorylation at Tyr1349 and downstream Thr202/Tyr204 phosphorylation of p44/42 MAP kinase. This HGF-induced signaling cascade was abolished by the c-Met inhibitor foretinib. Cell cycle analysis after foretinib treatment demonstrated enhanced G2 accumulation and increasing apoptosis within 72 h. Moreover, the IC50 of foretinib revealed 12.4 nM in SCCOHT-1 cells compared to 411 nM and 481 nM in NIH:OVCAR-3 and SK-OV-3 cells, respectively, suggesting potential therapeutic effects. Indeed, SCCOHT-1 and BIN-67 tumor xenografts in NODscid mice exhibited an approximately 10-fold and 5-fold reduced tumor size following systemic application of foretinib, respectively. Furthermore, foretinib-treated tumors revealed a significantly reduced vascularization and little if any c-Met-mediated signal transduction. Similar findings of reduced proliferative capacity and declined tumor size were observed after siRNA-mediated c-Met knock-down in SCCOHT-1 cells demonstrating that in vivo inhibition of these pathways contributed to an attenuation of SCCOHT tumor growth.


Recent progress of electrochemical hydrogen evolution over 1T-MoS2 catalysts.
Developing efficient and stable non-noble metal catalysts for the electrocatalytic hydrogen evolution reaction (HER) is of great significance. MoS2 has become a promising alternative to replace Pt-based electrocatalysts due to its unique layered structure and adjustable electronic property. However, most of the reported 2H-MoS2 materials are stable, but the catalytic activity is not very ideal. Therefore, a series of strategies such as phase modulation, element doping, defect engineering, and composite modification have been developed to improve the catalytic performance of MoS2 in the HER. Among them, phase engineering of 2H-MoS2 to 1T-MoS2 is considered to be the most effective strategy for regulating electronic properties and increasing active sites. Hence, in this mini-review, the common phase modulation strategies, characterization methods, and application of 1T-MoS2 in the HER were systematically summarized. In addition, some challenges and future directions are also proposed for the design of efficient and stable 1T-MoS2 HER catalysts. We hope this mini-review will be helpful to researchers currently working in or about to enter the field.


The triumph of the pre-embryo: interpretations of the human embryo in Parliamentary debate over embryo research.
In 1984, both British Houses of Parliament overwhelmingly condemned the proposal in the Warnock Report that research be allowed on human embryos, under licence, during the first two weeks of their existence. In 1990, legislation permitting such research and based directly on the Warnock proposal was approved with substantial majorities in the two Houses. This study describes some of the cultural developments underlying the swing within Parliament from almost total rejection of embryo research to eventual acceptance. Material taken from the parliamentary record and from the Warnock Report is used to illustrate how two competing images of the human embryo provided a central focus for the adversarial process whereby legislation on embryo research came to be enacted.


[Incidence of postoperative venous thromboembolism after thoracic surgery and its characteristic: a single center, prospective cohort study].
Objective: To evaluate the incidence of postoperative venous thromboembolism (VTE) after thoracic surgery and its characteristic. Methods: This was a single-center, prospective cohort study. Patients undergoing major thoracic surgeries between July 2016 and March 2017 at Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University were enrolled in this study. Besides the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower-extremity ultrasonography after surgery. CT pulmonary angiography (CTPA) was carried out if patients had one of the following conditions including typical symptoms of PE, high Caprini score (>9 points) or new diagnosed postoperative DVT. Caprini risk assessment model was used to detect high risk patients. No patients received any prophylaxis of VTE before surgery. Further data was analyzed for identifying the incidence of postoperative VTE. The t-test, χ2 test or Wilcoxon rank-sum test was used to analyze the quantitative data and classification data, respectively. Results: Totally 345 patients who undergoing major thoracic surgery were enrolled in this study including 145 benign diseases and 200 malignant diseases.There were 207 male and 138 female, aging from 15 to 85 years. Surgery procedures included 285 lung surgeries, 27 esophagectomies, 22 mediastinal surgeries and 11 other procedures. The overall incidence of VTE was 13.9% (48 of 345) after major thoracic surgery including 39 patients with newly diagnosed DVT (81.2%), 1 patient with PE (2.1%) and 8 patients with DVT+ PE (16.7%). The median time of VTE detected was 4.5 days postoperative. There were 89.6% (43/48) VTE cases diagnosed in 1 week. The incidence of VTE was 9.0% in patients with benign diseases, while 17.5% in malignant diseases (χ2=5.112, P<0.05). The incidence of VTE in patients with pulmonary diseases was 12.6%, among that, in patients with lung cancer and benign lung diseases was 16.4% and 7.5 % (χ2=4.946, P<0.05), respectively. Regarding to Caprini risk assessment model, the incidence of VTE in low risk patients, moderate risk patients (Caprini score 5 to 8 points)and high risk patients(≥9 points)were 0(0/77), 15.2%(33/217) and 29.4%(15/51), respectively(Z=-12.166, P<0.05). In patients with lung cancer, 98.2% of patients were moderate risk or high risk; only 3 cases scored low risk. The incidence of VTE in moderate risk and high risk patients was 13.4%(18/134) and 32.1%(9/28), respectively, while it was 0(0/3) in low risk patients. Conclusions: The overall incidence of VTE after major thoracic surgeries is 13.9%, and the incidence of VTE after lung cancer surgeries was 16.4%. Most of the VTE cases occurr within one week after the surgery. Caprini risk assessment model can identify high risk patients effectively.


Large-scale evaluation of a medical cross-language information retrieval system.
We propose an approach to multilingual medical document retrieval in which complex word forms are segmented according to medically relevant morpho-semantic criteria. At its core lies a multilingual dictionary, in which entries are equivalence classes of subwords, i.e. semantically minimal units. Using two different standard test collections for the medical domain, we evaluate our approach for six languages covered by our system.


Effects of nicosulfuron on plant growth and sugar metabolism in sweet maize (Zea mays L.).
The sulfonylurea herbicide nicosulfuron is efficient, harmless and selective at low doses and has been widely used in maize cultivation. In this study, a pair of corn sister lines, HK301 (nicosulfuron-tolerence, NT) and HK320 (nicosulfuron-sensitive, NS), was chosen to study the effect of nicosulfuron on plant growth and sugar metabolism in sweet maize (Zea mays L.) seedlings. All the experimental samples were subjected to treatment with water or 80 mg kg-1 of nicosulfuron when the sweet maize seedlings grew to the four-leaf stage. Nicosulfuron significantly inhibited the growth of NS line. The content of sucrose and the activities of sucrose phosphate synthase and sucrose synthase in the two inbred lines increased differentially under nicosulfuron stress compared with the respective control treatment. After nicosulfuron treatment, the activities of hexokinase and 6-phosphofructokinase and the contents of pyruvic acid and citric acid in NS line decreased significantly compared with those of NT line, while the content of sucrose and activities of sucrose phosphate synthase and sucrose synthase increased significantly. The disruption of sugar metabolism in NS line led to a lower supply of energy for growth. This study showed that the glycolysis pathway and the tricarboxylic acid cycle were enhanced in nicosulfuron-tolerant line under nicosulfuron stress in enhancing the adaptability of sweet maize.


Analysis of the interannual variation characteristics of the northernmost drift position of the green tide in the Yellow Sea.
The green tide in the Yellow Sea is the world's largest macroalgal bloom. The maximum area affected by green tide can reach tens of thousands of square kilometers. Previous studies have shown that green tide drifts northward during the outbreak, yet the location of its northernmost drift and the characteristics of interannual variations have not been explored in detail. In this paper, we use the Moderate Resolution Imaging Spectrometer (MODIS) data, GaoFen-1 (GF-1) satellite data, unmanned aerial vehicle (UAV) aerial data, and field trips for extraction and monitoring of green tide and then analyze the emergence, development, and dissipation of the green tide in Rongcheng coastal waters and the change of the northernmost drift position and its related factors from the year of 2013 to 2018. The results show that green tide have drifted to the Rongcheng coastal area over the years and the northernmost drift position can reach 37.662° N in 2014. Interannual difference of the northernmost position of the drift of the green tide is obvious, it is mainly affected by the wind, and there is no certain connection with the maximum coverage area, the coverage area when reaching the northernmost position, and the existence days of the green tide. These results can help to understand the drift range and dissipation process of green tide in the Yellow Sea.


General practitioner prescribing at first attendance for diseases.
Prescriptions written during first attendances of patients in the second quarter of the Australian GP Morbidity and Prescribing Survey (April-June, 1973), have been recorded and the results analysed. In the quarter, April-June, 1973, 186 general practitioners recorded data on all patients in a random week. The total number of attendances was 30,713.


Human systems integration in remotely piloted aircraft operations.
The role of humans in remotely piloted aircraft (RPAs) is qualitatively different from manned aviation, lessening the applicability of aerospace medicine human factors knowledge derived from traditional cockpits. Aerospace medicine practitioners should expect to be challenged in addressing RPA crewmember performance. Human systems integration (HSI) provides a model for explaining human performance as a function of the domains of: human factors engineering; personnel; training; manpower; environment, safety, and occupational health (ESOH); habitability; and survivability. RPA crewmember performance is being particularly impacted by issues involving the domains of human factors engineering, personnel, training, manpower, ESOH, and habitability. Specific HSI challenges include: 1) changes in large RPA operator selection and training; 2) human factors engineering deficiencies in current RPA ground control station design and their impact on human error including considerations pertaining to multi-aircraft control; and 3) the combined impact of manpower shortfalls, shiftwork-related fatigue, and degraded crewmember effectiveness. Limited experience and available research makes it difficult to qualitatively or quantitatively predict the collective impact of these issues on RPA crewmember performance. Attending to HSI will be critical for the success of current and future RPA crewmembers. Aerospace medicine practitioners working with RPA crewmembers should gain first-hand knowledge of their task environment while the larger aerospace medicine community needs to address the limited information available on RPA-related aerospace medicine human factors. In the meantime, aeromedical decisions will need to be made based on what is known about other aerospace occupations, realizing this knowledge may have only partial applicability.


Self-reported ongoing adherence to diet is associated with lower depression, fatigue, and disability, in people with multiple sclerosis.
Increasingly, dietary improvements have been shown to have positive associations with health outcomes in people with multiple sclerosis (pwMS). However, adhering to a MS-specific or high-quality diet may be a challenge. We therefore assessed the level of diet-adherence necessary to improve health outcomes of depression, fatigue, and disability. Data from an international population of pwMS followed over 7.5 years (n = 671) were analyzed. Self-reported diet quality via diet habits questionnaire (DHQ), and adherence to six MS-diets [Ashton Embry Best Bet, McDougall, Overcoming MS (OMS), Paleolithic (Paleo), Swank, and Wahls] were queried at two timepoints. Four levels of diet adherence were assessed: non-adherence at either timepoint; ceased at second timepoint; commenced at second timepoint; and ongoing at both timepoints. Associations between adherence to OMS and high-quality diet (DHQ score > median) with depression, fatigue, and disability, were assessed by log-binomial regression models adjusted for confounders. Forty-two percent of pwMS reported ongoing-adherence to a MS-diet at both timepoints, OMS (33%), Swank (4%), Wahls (1.5%), other (<1%). Of these, only OMS-diet adherence was analyzed for associations due to data availability. Ongoing-adherence to the OMS-diet or a high-quality diet, was associated with lower depression compared to non-adherence [OMS: Risk ratios (RR) = 0.80, p = 0.021; DHQ: RR = 0.78, p = 0.009] and ceased-adherence (OMS: RR = 0.70, p = 0.008; DHQ: RR = 0.70, p = 0.010), respectively. Ongoing-adherence to OMS-diet was associated with lower fatigue (RR = 0.71, p = 0.031) and lower severe disability (RR = 0.43, p = 0.033) compared to ceased-adherence. Results suggest potential benefits of adherence to the OMS- or a high-quality diet on MS health outcomes, with ongoing-adherence likely best. Diet modification and maintenance may serve as a point of intervention to manage MS symptoms, especially depression, in pwMS.


Mmp1 and Mmp2 cooperatively induce Drosophila fat body cell dissociation with distinct roles.
During Drosophila metamorphosis, the single-cell layer of fat body tissues gradually dissociates into individual cells. Via a fat body-specific RNAi screen in this study, we found that two matrix metalloproteinases (MMPs), Mmp1 and Mmp2, are both required for fat body cell dissociation. As revealed through a series of cellular, biochemical, molecular, and genetic experiments, Mmp1 preferentially cleaves DE-cadherin-mediated cell-cell junctions, while Mmp2 preferentially degrades basement membrane (BM) components and thus destroy cell-BM junctions, resulting in the complete dissociation of the entire fat body tissues into individual cells. Moreover, several genetic interaction experiments demonstrated that the roles of Mmp1 and Mmp2 in this developmental process are cooperative. In conclusion, Mmp1 and Mmp2 induce fat body cell dissociation during Drosophila metamorphosis in a cooperative yet distinct manner, a finding that sheds light on the general mechanisms by which MMPs regulate tissue remodeling in animals.


Successful treatment of 2 patients with brain metastases from non-small cell lung cancer with epidermal growth factor receptor mutation receiving dacomitinib: A case report.
Approximately 20% of patients with non-small cell lung cancer (NSCLC) are diagnosed with brain metastasis, which is related to poor survival outcomes. The ability of tyrosine kinase inhibitor drugs to penetrate the blood-brain barrier makes them a potential option for intracranial metastases. Dacomitinib, an irreversible second-generation pan-HER tyrosine kinase inhibitor, has become a standard therapy for patients with epidermal growth factor receptor mutations. However, its efficacy in patients with brain metastases (BMs) is not yet established. Here, we present 2 patients with epidermal growth factor receptor-mutant NSCLC with brain metastasis. After initiation of dacomitinib as first-line treatment, a significant clinical response was achieved, and a long-lasting complete remission was achieved in 1 patient up to this date. Case 1 was a 47-year-old man who was admittedtothe hospital because of recurrent cough and expectoration for >1 year. Chest computed tomography scans revealed a high-density shadow in the left upper lobe. Cranial magnetic resonance imaging indicated an abnormal nodular enhancement in the right cerebellar hemisphere. Case 2 was a 55-year-old man with a chief complaint of intermittent cough and expectoration for >1 month. Chest computed tomography revealed a high-density mass in the left superior lobe. Magnetic resonance imaging of the central nervous system revealed 2 abnormal nodular enhancements in the left frontal lobe. Both patients were diagnosed with lung adenocarcinoma by bronchoscopy and lymph node biopsy. Both patients received dacomitinib 30 mg once daily as first-line therapy for 8 and 11 months, respectively until disease progression. After treatment with dacomitinib, both patients achieved complete response in BMs. Progression-free survival was 11 and 8 months, respectively. Dacomitinib strongly controlled BMs in patients with advanced NSCLC, and the adverse reactions were tolerable. Dacomitinib may be considered a new treatment option for these patients. Further prospective studies are recommended to confirm this conclusion.


The unintended implications of blurring the line between research and clinical care in a genomic age.
While the development of next-generation sequencing technology has had a paradigm-changing impact on biomedical research, there is likely to be a gap between discovery of therapeutic benefits in research and actual adoption of the new technology into clinical practice. This gap can create pressure on the research enterprise to provide individualized care more typical of the clinic setting because it is uniquely accessible in research. This blurring of the line between research and clinical care is understandable, and perhaps even inevitable. But even if the gap is only transitory, such a blurring can have lasting implications, both by expanding obligations imposed on researchers, but also by challenging long-held ethical views. We explore this idea, focusing on how the dissolving distinction between research and clinical care has influenced the vigorous debate around how researchers should manage genetic findings (sometimes separated into primary and incidental or secondary findings) resulting from research.


[Mucocele of the sphenoid sinus].
Sphenoid sinus mucoceles are pseudocystic expansile slow-growing processes that arise within the sphenoid sinus. A dynamic process of bone resorption and erosion results in a pseudo-tumoral development. Clinical features and potential risks are related to mass effect with compression of the optic nerves and intracranial extension of the process. CT and MRI allow diagnosis and distinguish mucoceles from skull base tumors or inflammatory diseases. Endonasal endoscopic approach is adapted to the treatment of sphenoid mucoceles and allows marsupialization of the mucoceles.


Prevalence of oral mucosal lesions in an adult Iranian population.
Nowadays the importance of oral health to life quality is not obvious to anyone in our world. Oral lesions can interfere with daily social activities in involved patients through impacts on mastication, swallowing and speech and symptoms like xerostomia, halitosis or dysesthesia. To assess the prevalence and types of oral lesions in a general population in Rasht, Northern Province of Iran. 1581 people aged > 30 years old who were inhabitant of Rasht, Iran, enrolled in a cross-sectional study. For each individual a detailed questionnaire based on the world health organization (WHO) guidelines in order to diagnosis of the lesions was filled and it contained all the required data. Participants were divided into two groups with and without oral mucosal lesions and oral mucosal lesions were divided into two groups with and without. Demographic characteristics and clinical information including age, sex, smoking (cigarette and tobacco), opium consumption, medication and oral and dental hygiene were collected and compared between these two groups. The prevalence of mucosal lesions in our study was 19.4%. Our data demonstrated higher prevalence of oral mucosal lesions in males and young adults (30-40 years). The most common mucosal lesion among our participants was Fissured tongue(4%), followed by Fordyce granules(2.8%), geographic tongue(2.6%) , Pigmentation(2.5%), Candida(1.8%), Smoker Plate(1.6%), lingual Varices(1.5%), Petechiae(1.4%) and lingual labial(1.4%) . Leukoplakia was observed only in two people (0.1%).No case of malignant lesions was detected. No statistically significant difference was confirmed between the two groups regarding smoking, opium consumption, medication and oral and dental hygiene. Our data has provided baseline information about epidemiologic aspects of oral mucosal lesions which can be valuable in organized national program targeting on oral health and hygiene in the society.


Is restoration of vertebral body height after vertebral body fractures and minimally-invasive dorsal stabilization with polyaxial pedicle screws just an illusion?
Thoracolumbar spine fractures often require surgical treatment as they are associated with spinal instability. Optimal operative techniques and treatment are discussed controversially. Aim of our prospective cohort study was to investigate the sagittal alignment after reduction, the secondary loss of reduction and the subjective outcome as well as the causal correlation of these parameters after minimally invasive stabilization of thoracic and lumbar fractures with polyaxial pedicle screws. In a single-center study, a total of 78 patients with an average age of 61 ± 17 years who suffered a fracture of the thoracic or lumbar spine were included and subjected to a clinical and radiological follow-up examination after 8.5 ± 8 months. The kyphotic deformity was measured by determining the vertebral body angle, the mono- and bi-segmental wedge angle at three time points. The patients' subjective outcome was evaluated by the VAS spine score. After surgical therapy, a significant reduction of the traumatic kyphotic deformity was shown with an improvement of all angles (vertebral body angle: 3.2° ± 4.4°, mono- and bi-segmental wedge angle: 3.1° ± 5.6°, 2.0° ± 6.3°). After follow-up, a significant loss of sagittal alignment was observed for all measured parameters with a loss of correction. However, no correlation between the loss of reduction and the subjective outcome regarding the VAS spine scale could be detected. The minimally invasive dorsal stabilization of thoracic and lumbar spine fractures with polyaxial pedicle screws achieved a satisfactory reduction of the fracture-induced kyphotic deformity immediately postoperatively with a floss of reduction in the further course. However, maybe the main goal of this surgical procedure should be the prevention of a complete collapse of the vertebral body instead of a long-lasting restoration of anatomic sagittal alignment. II.


Synthesis of (-)-pinolidoxin: divergent synthetic strategy exploiting a common silacyclic precursor.
[reaction: see text] We describe a highly convergent and efficient synthesis of (-)-pinolidoxin, a potent modulator of plant pathogenesis, providing unambiguous determination of the relative and absolute stereostructure of this highly oxygenated fungal metabolite. Our unique strategy highlights the applications of novel silacyclic precursors for stereocontrolled polyol synthesis and features the finding of the reversible ring-closing metathesis.


The Role of Molybdenum Oxysulfide Rings in the Formation of Two-Dimensional Molybdenum Disulfide by Powder Vaporization.
Sulfurization of molybdenum trioxide by elemental sulfur through powder vaporization is a common method used for growth of molybdenum disulfide. Optimization of complexes between sulfur allotropes and molybdenum species using Density Functional Theory has revealed the molecular mechanism of sulfurization. Complete sulfurization of molybdenum trioxide to molybdenum disulfide requires at least three sets of nucleophilic addition-elimination reactions that generate the experimentally observed molybdenum oxysulfide intermediates along the reaction pathway. Each nucleophilic addition reaction of a sulfur allotrope to a molybdenum species gives rise to a molybdenum oxysulfide ring, which can dissociate into a more sulfurized molybdenum intermediate. At the typical growth temperatures used in powder vaporization, the equilibrium constants for these reactions are essentially unity. Thus, sulfurization is driven by excess sulfur and gas flow through the growth furnace.


Lifestyles of nursing students from a Colombian public university.
To assess the lifestyles of nursing students from a Colombian public university. A cross-sectional study was conducted in 2014. 380 students answered by self-reporting the adapted version in Spanish of FANTASTIC Lifestyles Assessment Questionnaire of Wilson and Ciliska. Lifestyles were poor in 9.2%, fair in 31.3%, good in 53.7%, and excellent in only 5.8% of the participants. Statistically-significant differences of the total mean score were not found when comparing with gender, age group, and course year, but were detected in two domains by gender: a) physical activity (higher score in men) and b) cigarette smoking (higher score in women). An important proportion of our nursing students has inadequate lifestyles, which means deferred risks for the development of chronic diseases. Universities should promote the training of the future professionals in nursing with knowledge and skills aimed at healthy lifestyles.


Cellular, immunologic and biochemical characterization of topical retinoic acid-treated human skin.
Histologic and clinical improvement of sun-exposed skin following topical treatment with retinoic acid has been reported. Daily application of retinoic acid typically results within 2-5 d in an erythematous scaling reaction, which lessens with continued usage. The cellular, immunologic, and biochemical basis of this retinoid reaction and its role in the repair of photodamaged skin are not known. To investigate the retinoid reaction in man, we have treated non-sun-exposed skin with 0.1% retinoic acid cream (Retin-A, Ortho Pharmaceutical Corporation, Raritan, NJ) under occlusion for 4 d to induce erythema and then examined changes in 1) histology, 2) expression of cell-surface molecules, 3) the enzymes and second messengers of the phospholipase C/protein kinase C signal-transduction system, 4) levels of eicosanoids, and 5) levels of interleukin-1 protein and mRNA. These parameters were chosen for measurement both because they are indicators of epidermal function and previous studies suggest they may be responsive to retinoic acid treatment. Epidermal cell growth as judged by increased epidermal thickness and mitotic figures was significantly increased in retinoic acid-treated skin compared to vehicle-treated controls. Increased numbers of CD4+ T cells accompanied by prominence of dermal dendrocytes in the papillary dermis and focal keratinocyte expression of intercellular adhesion molecule-1 were observed in retinoic acid-treated biopsies. Phosphoinositide-specific phospholipase C activity and 1,2-diacylglycerol content were also elevated in retinoic acid-treated epidermis. Protein kinase C activity was reduced by one third in both the soluble and membrane fraction, suggesting down-regulation. Surprisingly, in view of the inflammatory nature of the retinoid reaction, no increases were observed in arachidonic acid, its metabolites, interleukin-1 alpha, or interleukin-1 beta. To examine the specificity of the retinoid reaction, subjects were treated with the irritant sodium lauryl sulfate, under conditions that resulted in a reaction clinically similar to that observed with retinoic acid. The histologic alterations induced by sodium lauryl sulfate were found to be indistinguishable from those induced by retinoic acid. These data indicate that, although a wide range of cellular and molecular alterations occur in retinoic acid-treated skin, these changes may not be necessarily specific or unique for retinoic acid.


Growth of mouse megakaryocyte colonies in vitro.
Mouse bone marrow and spleen cells formed pure or mixed colonies of up to 80 megakaryocytes in agar cultures after stimulation by medium conditioned by activated mouse lymphoid cells. Megakaryocytes were identified on the basis of their morphology, polyploid mitoses and DNA content, and high cytoplasmic content of acetylcholinesterase. Megakaryocyte colony-forming cells were relatively small with a peak sedimentation velocity of 4.2 mm/hr. Spleen, lymph node, and thymus cells produced the factor stimulating megakaryocyte proliferation after culture in medium containing 2-mercaptoethanol, with or without added mitogens or allogeneic spleen cells. Peak activity in conditioning medium was associated with the small lymphocyte fractions in mouse spleen.


Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma.
Bortezomib and melphalan have synergistic effects against multiple myeloma (MM) cells. We conducted a pilot study on the combination of bortezomib and high-dose melphalan (Bor-HDM) as a conditioning regimen followed by autologous stem cell transplant (ASCT) in 17 Japanese patients with newly diagnosed MM, in comparison with a historical control of patients who received high-dose melphalan (HDM) only followed by ASCT. Nine patients received a single dose of bortezomib 1.3 mg/m(2) on day -1 in combination with melphalan 100 mg/m(2) on days -3 and -2 (Bor1-HDM), and eight received two doses of bortezomib 1.3 mg/m(2) on days -4 and -1 (Bor2-HDM) in combination with HDM. Engraftment of autologous peripheral blood stem cells and regimen-related toxicities (RRT) were comparable among the HDM and Bor-HDM groups. Probability of upgrading from a less than very good partial response (VGPR) to VGPR after ASCT was approximately two times higher in the Bor-HDM group than in the HDM group. However, we observed no significant differences in engraftment, RRT, and response rates between the Bor1-HDM and Bor2-HDM groups. The present study showed that concurrent administration of at least two doses of bortezomib in combination with HDM can be safe in Japanese patients. Additional large prospective randomized trials are required to address the optimal dosages and schedules of bortezomib administration, as well as the efficacy of the Bor-HDM conditioning regimen for ASCT.


Effect of chronic treatment with angiotensin I converting enzyme inhibitors on circulating atrial natriuretic polypeptide in spontaneously hypertensive rats.
We have recently shown that circulating atrial natriuretic polypeptide (ANP) in adult spontaneously hypertensive rats (SHR) is higher than that in age-matched Wistar-Kyoto rats (WKY). The present experiment was designed to examine the possible effects of chronic treatment with angiotensin I converting enzyme inhibitors (ACEI) on plasma ANP levels in SHR. Captopril and enalapril lowered blood pressure and reduced relative ventricular weight in SHR but not to the level of WKY. Plasma ANP levels were decreased by captopril and enalapril compared with untreated SHR. These results suggest that the ANP release may be suppressed in ACEI-treated SHR compared with untreated SHR. We speculate that a reduction of cardiac overload by ACEI may in part explain the decline of circulating ANP.


Shuttle vector-based transformation system for Pyrococcus furiosus.
Pyrococcus furiosus is a model organism for analyses of molecular biology and biochemistry of archaea, but so far no useful genetic tools for this species have been described. We report here a genetic transformation system for P. furiosus based on the shuttle vector system pYS2 from Pyrococcus abyssi. In the redesigned vector, the pyrE gene from Sulfolobus was replaced as a selectable marker by the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (HMG-CoA) conferring resistance of transformants to the antibiotic simvastatin. Use of this modified plasmid resulted in the overexpression of the HMG-CoA reductase in P. furiosus, allowing the selection of strains by growth in the presence of simvastatin. The modified shuttle vector replicated in P. furiosus, but the copy number was only one to two per chromosome. This system was used for overexpression of His(6)-tagged subunit D of the RNA polymerase (RNAP) in Pyrococcus cells. Functional RNAP was purified from transformed cells in two steps by Ni-NTA and gel filtration chromatography. Our data provide evidence that expression of transformed genes can be controlled from a regulated gluconeogenetic promoter.


Accuracy improvement for identifying translation initiation sites in microbial genomes.
At present the computational gene identification methods in microbial genomes have a high prediction accuracy of verified translation termination site (3' end), but a much lower accuracy of the translation initiation site (TIS, 5' end). The latter is important to the analysis and the understanding of the putative protein of a gene and the regulatory machinery of the translation. Improving the accuracy of prediction of TIS is one of the remaining open problems. In this paper, we develop a four-component statistical model to describe the TIS of prokaryotic genes. The model incorporates several features with biological meanings, including the correlation between translation termination site and TIS of genes, the sequence content around the start codon; the sequence content of the consensus signal related to ribosomal binding sites (RBSs), and the correlation between TIS and the upstream consensus signal. An entirely non-supervised training system is constructed, which takes as input a set of annotated coding open reading frames (ORFs) by any gene finder, and gives as output a set of organism-specific parameters (without any prior knowledge or empirical constants and formulas). The novel algorithm is tested on a set of reliable datasets of genes from Escherichia coli and Bacillus subtillis. MED-Start may correctly predict 95.4% of the start sites of 195 experimentally confirmed E.coli genes, 96.6% of 58 reliable B.subtillis genes. Moreover, the test results indicate that the algorithm gives higher accuracy for more reliable datasets, and is robust to the variation of gene length. MED-Start may be used as a postprocessor for a gene finder. After processing by our program, the improvement of gene start prediction of gene finder system is remarkable, e.g. the accuracy of TIS predicted by MED 1.0 increases from 61.7 to 91.5% for 854 E.coli verified genes, while that by GLIMMER 2.02 increases from 63.2 to 92.0% for the same dataset. These results show that our algorithm is one of the most accurate methods to identify TIS of prokaryotic genomes. The program MED-Start can be accessed through the website of CTB at Peking University: http://ctb.pku.edu.cn/main/SheGroup/MED_Start.htm.


[Effects of Crude Atractylodis Rhizoma and Processed Atractylodis Rhizoma on AQP1 - AQP5 and Hemorheology in Healthy Rats].
To study the different effects of crude Atractylodis Rhizoma and processed Atractylodis Rhizoma in healthy rats, in order to prove the traditional theory that the crude Atractylodis Rhizoma has dry effects and the dry effects can be weaken by processing. Health rats had been orally administered with pure water, crude Atractylodis Rhizoma, processed Atractylodis Rhizoma and atropine. The concentration of AQP1 and AQP5 in submaxillary gland were measured by ELISA. Their index of submaxillary gland, hemorheology and moisture content of intestine were also measured. There were obvious differences of concentration of AQP1 and AQP5 in submaxillary gland, index of submaxillary gland, hemorheology and moisture content of intestine between the rats which had been orally administered crude Atractylodis Rhizoma and the rats administered processed Rhizoma Atractylodes. The dry effects of Atractylodis Rhizoma works on rats' moisture content of intestine, index of submaxillary gland and hemorheology. The dry effects can be weaken by processing.


Differential functional activity of 5-hydroxytryptamine receptor ligands and beta adrenergic receptor antagonists at 5-hydroxytryptamine1B receptor sites in Chinese hamster lung fibroblasts and opossum renal epithelial cells.
Functional activity of 5-hydroxytryptamine (5-HT) receptor ligands and beta adrenergic receptor antagonists was studied at 5-HT1B receptor sites in Chinese hamster lung (CHL) fibroblasts by measuring two cellular responses: inhibition of forskolin-stimulated cyclic AMP formation and potentiation of basic fibroblast growth (BFGF) induced mitogenesis. A good correlation was found between the potency of agonists to inhibit forskolin-induced cyclic AMP formation and their potency to potentiate bFGF-induced thymidine incorporation in CHL fibroblasts. Potent agonist activity was measured with 5-methoxy-3,1,2,3,6-tetrahydro-4-pyidinyl- 1H-indole (RU 24,969), 5-carboxamidotryptamine (5-CT), 3-(1,2,5,6)-tetrahydro-4-pyridyl-5-pyrrolo(3,2-b)pyril-5-one (CP 93,129) and 5-HT, whereas sumatriptan displayed weak agonist activity at concentrations different from its binding affinity for 5-HT1B binding sites. In contrast to the observed 5-HT1B receptor-mediated agonist activity in opossum kidney cells for metergoline and the beta adrenergic receptor antagonists: cyanopindolol, 4-(3-tert-butyl-amino-2-hydroxypropoxy)-indole-2 carbonic acid isopropyl ester (SDZ 21,009), isamoltane, (-)-propranolol and (-)-pindolol, antagonist activity at 5-HT1B receptor sites was yielded in CHL fibroblasts in accordance with the reported observations at rat brain 5-HT1B receptors. Methiothepin was the only compound that antagonized both the opossum kidney cell and CHL fibroblast 5-HT1B receptor-mediated responses although the antagonist effect was more pronounced in CHL fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)


Surgical treatment of intramedullary spinal cord tumors: prognosis and complications.
Retrospective case series. To evaluate our recent treatment strategy for intramedullary spinal cord tumors. Department of Orthopaedic Surgery, Keio University, Japan. We reviewed 68 cases of intramedullary tumors (ependymoma, 33; astrocytoma, 23; hemangioblastoma, 12), treated surgically between 1994 and 2003. There were 42 males and 26 females whose mean age at the time of surgery was 43 years. The mean follow-up period was 6.2 years. The tumor malignancy grade according to the WHO classification was astrocytoma grade I, 3; grade II, 8 (low-grade: 11 cases); grade III, 10; grade IV, 2 (high-grade: 12 cases). All ependymomas were grade II. Three of the 12 hemangioblastomas were associated with von Hippel-Lindau disease. Total excision was achieved in 90% of the ependymomas and functional improvement was obtained when the preoperative neurological deficit was mild. Approximately 50% of low-grade astrocytomas could be totally excised with favorable survival outcomes, suggesting that total excision should be attempted for low-grade astrocytomas. However, total excision of high-grade tumors was difficult and the functional outcomes were poor. Cordotomy should be considered in patients with a thoracic high-grade astrocytoma. Total resection was possible in 92% of hemangioblastoma, and the functional outcomes were good, however, more attention should be paid for tumors with feeding arteries on the ventral side and for those associated with von Hippel-Lindau disease. Predictors of good surgical outcome for intramedullary spinal cord tumors were histological grades of the tumors, surgical margins, and neurological status of the patient before surgery.


An anthropological analysis of European Union (EU) health governance as biopolitics: the case of the EU tissues and cells directive.
Healthcare in Europe is increasingly influenced by European Union (EU) regulation enacted to harmonise heterogeneous practices through common safety standards. In many instances directives on safety issues evade public debate because they are seen as merely 'technical matters'. In this paper I analyse the implications at a national level in Denmark of one such piece of legislation: the EU Tissues and Cells Directive. The analysis is based on participant observation, interviews and document analysis conducted in the period from May 2007 to June 2009. I follow translations of the Directive from the level of the EU text into national legislation and further into everyday practices. From a biopolitical perspective, I explore the implications of this so-called technical directive that appear necessary for policymakers and yet remain strangely detached from the everyday experiences of people for whom and on whom it is supposed to work. The Directive has serious implications for the allocation of funds, for patients and for healthcare professionals. These implications need to be discussed. Even more basically, the analysis points to a need for discussing what makes so-called technical directives necessary. This article is intended to facilitate this type of debate.


Solid Solution Metal Chalcogenides for Sodium-Ion Batteries: The Recent Advances as Anodes.
The sodium-ion battery (SIB) has attracted ever growing attention as a promising alternative of the lithium-ion battery (LIB). Constructing appropriate anode materials is critical for speeding up the application of SIB. This review aims at guiding anode design from the material's perspective, and specifically focusing on solid solution metal chalcogenide anode. The sodium ion storage mechanisms of a solid solution metal chalcogenide anode is overviewed on basis of the elements it is composed of, and discusses how the solid solution character alters the electrochemical performances through diffusion and surface-controlled processes. In addition, by classifying solid solution metal chalcogenide as cation and anion, their recent applications are updated, and understanding the roles of guest elements in improving the electrochemical behaviors of a solid solution metal chalcogenide is carried out. After that, discussion of possible strategies to further optimize these anode materials in the future, flowing from crystal structure design to morphology control and finally to the intimacy improvement between conductive matrix and solid solution metal chalcogenide are also provided.


Sepsis Strengthens Antagonistic Actions of Neostigmine on Rocuronium in a Rat Model of Cecal Ligation and Puncture.
The antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP). A total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction. Four of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET). Sepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.


Dynamic tunneling force microscopy for characterizing electronic trap states in non-conductive surfaces.
Dynamic tunneling force microscopy (DTFM) is a scanning probe technique for real space mapping and characterization of individual electronic trap states in non-conductive films with atomic scale spatial resolution. The method is based upon the quantum mechanical tunneling of a single electron back and forth between a metallic atomic force microscopy tip and individual trap states in completely non-conducting surface. This single electron shuttling is measured by detecting the electrostatic force induced on the probe tip at the shuttling frequency. In this paper, the physical basis for the DTFM method is unfolded through a physical model and a derivation of the dynamic tunneling signal as a function of several experimental parameters is shown. Experimental data are compared with the theoretical simulations, showing quantitative consistency and verifying the physical model used. The experimental system is described and representative imaging results are shown.


Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor.
The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5(+)/6(+)) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients.


Induction of Non-Apoptotic Cell Death by Adrenergic Agonists in Human Oral Squamous Cell Carcinoma Cell Lines.
Although adrenergic agonists have been used in dental treatments and oral surgery for general anesthesia, their cytotoxicity against human oral malignant and non-malignant cell has not been well- understood. The present study was undertaken to investigate the cytotoxicity of five adrenergic agonists against human oral squamous cell carcinoma (OSCC), glioblastoma, promyelocytic leukemia, and normal oral mesenchymal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) and normal epidermal keratinocytes. Tumor-specificity (TS) was calculated by the ratio between the mean 50% cytotoxic concentration against normal cells to that of tumor cells. Internucleosomal DNA fragmentation was detected using agarose gel electrophoresis. Caspase-3 activity was measured by substrate cleavage. Both cytotoxicity and tumor-specificity of adrenergic agonists against OSCC cell lines was in the order of isoprenaline>dexmedetomidine> adrenaline>clonidine and phenylephrine. Isoprenaline and dexmedetomidine did not induce apoptosis markers, such as internucleosomal DNA fragmentation and caspase-3 activation, but induced a smear pattern of DNA fragmentation in OSCC cell lines. Their cytotoxicity was not reduced by pretreatment with autophagy inhibitors, or by adrenoceptors antagonists. Addition of superoxide dismutase and catalase significantly reduced the cytotoxicity of isoprenaline, but not that of dexmedetomidine. Isoprenaline and dexmedetomidine induce non-apoptotic cell death by different mechanisms.


In their own words: using narratives to teach gerontology.
In narrative constructed in conversations, older adults often present "small stories". These narrative fragments provide extensive information about their experiences, values, and aspects of their lives that can be used to help learners understand key concepts about aging and the life course. The authors provide an overview of approaches including exercises and activities keyed to a corpus of oral narratives, targeting graduate and undergraduate students.


The Effectiveness of Family Constellation Therapy in Reducing Psychopathological Symptoms in a Naturalistic Setting.
The aim of this study (ClinicalTrials.gov identifier: NCT03233958) was to provide further evidence on the effectiveness and safety of family/systemic constellation therapy, a widely used but rarely investigated form of brief group psychotherapy. Altogether, 102 individuals from the general population were followed up 1- and 6 months after their participation in the 2-day intervention. Indicators of general and problem-area-specific psychopathology, interpersonal quality of life, meaning in life, and general wellbeing were assessed. Both statistical and clinical significance were considered, and active surveillance of potential iatrogenic effects was also conducted. The data showed significant improvement post-intervention in the case of the vast majority of the 17 outcome variables. At 1-month follow-up, the magnitude of improvements was typically in the moderate range. The patterns were very similar at the 6-month follow-up, suggesting that most intervention benefits were sustained in the middle term. Sensitivity analyses showed no therapist effects across the three intervention providers. Analyses into clinical significance showed that the most reliable improvements occurred in relation to interpersonal quality of life and non-diagnosis-specific psychopathology, with approximately half of the participants showing reliable improvement. Iatrogenic effects were comparable - both in terms of frequency and severity - to those reported for other forms of psychotherapy. Findings of the present study point toward the safety and effectiveness of family constellation therapy in reducing a variety of psychopathological symptoms (e.g., depression and anxiety) and increasing general well-being. This effectiveness is especially remarkable when considering the brevity and cost-effectiveness of the intervention.


Computational enzymology: insight into biological catalysts from modelling.
Molecular modelling and simulation can give atomic-level understanding of the fundamental mechanisms of enzyme catalysis. For example, modelling can identify likely enzyme reaction mechanisms, analyse catalytic interactions, and identify determinants of reactivity and specificity. Combined quantum mechanics/molecular mechanics (QM/MM) methods are an important technique in this maturing field of computational enzymology. By coupling quantum chemical (electronic structure) calculations on the active site with a simpler, empirical 'molecular mechanics' treatment of the rest of the protein, QM/MM methods allow the modelling of reactions in enzymes. In this Highlight, QM/MM techniques are outlined and some recent applications are discussed. These applications illustrate how calculations of this type can be used to interpret and complement experiments, with important potential implications for practical developments such as drug and catalyst design.


An antifungal protein from the marine bacterium streptomyces sp. Strain AP77 is specific for Pythium porphyrae, a causative agent of red rot disease in Porphyra spp.
A novel antifungal protein (SAP) was found in the culture supernatant of a marine bacterium, Streptomyces sp. strain AP77, and was purified. This protein was characterized by chemical, biochemical, and biological analyses. By using gel filtration, the molecular mass of SAP was estimated to be 160 kDa. Structural analysis of SAP by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry suggested that SAP is composed of three heterologous protein subunits of 41.7 kDa (SAP1), 21.7 kDa (SAP2), and 18.7 kDa (SAP3) at a molar ratio of 1:1:5 (or 1:1:6). N-terminal amino acid sequence analysis and a homology search revealed that SAP1, SAP2, and SAP3 exhibit 64.3, 68.4, and 86.7% similarity to three Streptomyces coelicolor polypeptides, puromycin resistance protein (Pur8), a conserved hypothetical protein, and bacterioferritin, respectively. The MIC of purified SAP against Pythium porphyrae was determined to be 1.6 microg/disk, whereas no inhibitory effect was observed at concentrations up to 100 microg/disk against most of the fungal and bacterial strains tested; the only exception was relatively strong antifungal activity against Pythium ultimum (MIC, 6.3 microg/disk). In vitro and in vivo toxicity tests demonstrated that SAP showed no toxicity against Porphyra yezoensis cells, human normal dermal fibroblasts, and mice at doses up to 700 microg/ml (for 24 h), 250 microg/ml (for 12 h), and 75 mg/kg (for 35 days), respectively. SAP was labile when it was subjected to a heated-air drying treatment, which is a great advantage in food production procedures. These results indicated that Streptomyces sp. strain AP77 might be useful as a gene source for safe transgenic Porphyra breeding for tolerance to Pythium infection.


Diverse xenotropic virus expressions in two NZB mouse breeding lines that differ in chromosome breakage.
Two breeding lines of the NZB/BI mouse strain, which was originated from Bielschowsky's stock and maintained as a conventional inbred colony since 1963, were developed by selective matings according to chromosome breakage incidence in bone marrow cells. These breeding lines were used because they represent an interesting experimental model, since they differ in the manifestations of the autoimmune process and the incidence of lymphomas. The present study showed that embryos from both breeding lines differed in the expression of the xenotropic type C RNA virus, characteristic of NZB mice. All 17 cultures initiated with embryos from the line showing high chromosome breakage (HB) had positive reverse transcriptase (RT) reactions after cocultivation with an indicator cell line (SIRC). On the contrary, only 3 of the 22 embryos from the line showing low chromosome breakage (LB) had RT activity at late passages (7-10). The chromosome studies done on these embryo cultures showed highly significant differences in the chromosome breakage incidence for the 2 breeding lines [10.6 and 20.5% of cells with aberrations for LB and HB embryos, respectively (P less than 0.001)].


Relational event models for longitudinal network data with an application to interhospital patient transfers.
The main objective of this paper is to introduce and illustrate relational event models, a new class of statistical models for the analysis of time-stamped data with complex temporal and relational dependencies. We outline the main differences between recently proposed relational event models and more conventional network models based on the graph-theoretic formalism typically adopted in empirical studies of social networks. Our main contribution involves the definition and implementation of a marked point process extension of currently available models. According to this approach, the sequence of events of interest is decomposed into two components: (a) event time and (b) event destination. This decomposition transforms the problem of selection of event destination in relational event models into a conditional multinomial logistic regression problem. The main advantages of this formulation are the possibility of controlling for the effect of event-specific data and a significant reduction in the estimation time of currently available relational event models. We demonstrate the empirical value of the model in an analysis of interhospital patient transfers within a regional community of health care organizations. We conclude with a discussion of how the models we presented help to overcome some the limitations of statistical models for networks that are currently available. Copyright © 2017 John Wiley & Sons, Ltd.


Ovarian response to exogenous gonadotropins in women with elevated serum prolactin.
To determine if elevated serum prolactin hPRL inhibits ovarian steroidogenesis and contributes to the amenorrhea associated with galactorrhea syndromes, the following study was performed. Four women with amenorrhea, galactorrhea, and elevated serum hPRL levels were treated with menopausal gonadotropins (Pergonal) for the associated infertility. Urinary estrogen response was comparable to that in normal ovulatory women in each patient. Ovulation occurred in 3 of the 4 women with resultant conception and normal pregnancies. There was no evidence to support the contention that elevated hPRL interferes with ovarian function.


Theoretical Study on the Photoemission Performance of a Transmission Mode In0.15Ga0.85As Photocathode in the Near-Infrared Region.
Benefiting from a high quantum efficiency, low thermal emittance, and large absorption coefficient, InxGa1-xAs is an excellent group III-V compound for negative electron affinity (NEA) photocathodes. As the emission layer, InxGa1-xAs, where x = 0.15, has the optimal performance for detection in the near-infrared (NIR) region. Herein, an NEA In0.15Ga0.85As photocathode with Al0.63Ga0.37As as the buffer layer is designed in the form of a transmission mode module. The electronic band structures and optical properties of In0.15Ga0.85As and Al0.63Ga0.37As are calculated based on density functional theory. The time response characteristics of the In0.15Ga0.85As photocathode have been fully investigated by changing the photoelectron diffusion coefficient, the interface recombination velocity, and the thickness of the emission layer. Our results demonstrate that the response time of the In0.15Ga0.85As photocathode can be reduced to 6.1 ps with an incident wavelength of 1064 nm. The quantum efficiency of the In0.15Ga0.85As photocathode is simulated by taking into account multilayer optical thin film theory. The results indicate that a high quantum efficiency can be obtained by parameter optimization of the emission layer. This paper provides significant theoretical support for the applications of semiconductor photocathodes in the near-infrared region, especially for the study of ultrafast responses in the photoemission process.


The Meaning of Intraoperative Errors: Perioperative Nurse Perspectives.
Medical errors involve different health care professionals, are multifaceted, and can occur at the individual practitioner or system level. The conditions for errors vary in the health care environment; some practice areas may be more vulnerable to errors than others. Limited research exists that explores perioperative nursing errors. The purpose of this study was to describe and interpret the experiences of perioperative nurses related to intraoperative errors. We used the hermeneutic phenomenological method. Ten perioperative RNs participated in focus group interviews that we audio-recorded and transcribed. We analyzed data using thematic analysis, and three themes emerged that represent the essence of the experience of nurses involved in intraoperative errors: environment, being human, and moving forward. The findings support efforts to improve quality care and foster a culture of safety in the OR through strategies such as perioperative staff training, interprofessional team building, and controlling environmental factors that are distracting.


Electron temperature of ultracold plasmas.
We study the evolution of ultracold plasmas by measuring the electron temperature. Shortly after plasma formation, competition between heating and cooling mechanisms drives the electron temperature to a value within a narrow range regardless of the initial energy imparted to the electrons. In agreement with theory predictions, plasmas exhibit values of the Coulomb coupling parameter Gamma less than 1.


Water and energy linkages for groundwater exploitation: a case study of Gujarat State, India.
Water and energy, two important resources for human development, have inextricable interlinkages between them. Their complementarity, a blessing otherwise, causes a vicious cycle in a complex situation like the present case study of Gujarat State, India. This paper analyses the demand-supply situation of both sectors for a State that is primarily agrarian but also with a high industrial growth rate. Due to inequitable distribution of surface water, recurrent droughts and ever increasing demand trend, groundwater (a major source in the State) has been overexploited in many parts, leading to 'water mining' with worsening water quality. With more than 40% energy consumed for extracting groundwater, this has had a serious impact on the energy balance. The paper discusses the energy requirements to satisfy the water needs and the water requirements for generation of energy. Finally, the feasible options available to meet the crisis, ranging from development of mega projects like Sardar Sarovar and Kalpasar to micro water harvesting structures, water pricing, consumer training etc., are reviewed.


Different approach to medical decision-making in difficult circumstances: Kittay's Ethics of Care.
The onset of the COVID-19 pandemic has necessitated advances in bioethical approaches to medical decision-making. This paper develops an alternative method for rationing care during periods of resource scarcity. Typical approaches to triaging rely on utilitarian calculations; however, this approach introduces a problematic antihumanist sentiment, inviting the proposition of alternative schemata. As such, we suggest a feminist approach to medical decision-making, founded in and expanding upon the framework of Eva Kittay's Ethics of Care. We suggest that this new structure addresses the issue of medical decision-making during times of resource scarcity just as well as pure utilitarian approaches while better attending to their significant theoretical concerns, forming a coherent alternative to the current bioethical consensus.


[When gluten-free diet does not cure celiac disease].
Dietary deviations and continuous usage of gluten even in small amounts are the most common causes of poor treatment response for celiac disease. In rare refractory celiac disease symptoms and small bowel mucosal morphological damage do not heal despite a strict diet. In such cases it is important to distinguish between type I and II refractory celiac disease by using small bowel lymphocyte markers and clonality of inflammatory cells. Increased risk of small intestinal lymphoma is especially associated with type II disease, which has a poorer prognosis. Type I is often treated with corticosteroids and azathioprine.


Refractory anaemia and mitochondrial cytopathy in childhood.
We report two cases of childhood myelodysplasia (MDS) related to a mitochondrial (mt) cytopathy that illustrate the difficulty in recognizing such disorders in patients with solely haematological signs. Both patients have refractory anaemia with ring sideroblasts and vacuolization of haemopoietic precursors. These cytological features are similar to those observed in Pearson's disease, recently identified as a mitochondrial disease, and are strongly suggestive of a mitochondrial enzyme defect. The diagnosis of mitochondrial cytopathy was established on Southern blotting of mt DNA, showing a mt DNA deletion, or on the impairment of the respiratory chain enzyme activities. The absence of cytogenic abnormalities, and the polyclonal pattern of peripheral neutrophil and lymphocyte fractions, suggest that, in mt cytopathies, MDS cannot be considered as a truly malignant disorder.


Polarization of M2 Macrophages by Interaction between Prostate Cancer Cells Treated with Trichomonas vaginalis and Adipocytes.
Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.


Computational approach for structure generation of anisotropic particles (CASGAP) with targeted distributions of particle design and orientational order.
The macroscopic properties of materials are governed by their microscopic structure which depends on the materials' composition (i.e., building blocks) and processing conditions. In many classes of synthetic, bioinspired, or natural soft and/or nanomaterials, one can find structural anisotropy in the microscopic structure due to anisotropic building blocks and/or anisotropic domains formed through the processing conditions. Experimental characterization and complementary physics-based or data-driven modeling of materials' structural anisotropy are critical for understanding structure-property relationships and enabling targeted design of materials with desired macroscopic properties. In this pursuit, to interpret experimentally obtained characterization results (e.g., scattering profiles) of soft materials with structural anisotropy using data-driven computational approaches, there is a need for creating real space three-dimensional structures of the designer soft materials with realistic physical features (e.g., dispersity in building block sizes) and anisotropy (i.e., aspect ratios of the building blocks, their orientational and positional order). These real space structures can then be used to compute and complement experimentally obtained characterization results or be used as initial configurations for physics-based simulations/calculations that can then provide training data for machine learning models. To address this need, we present a new computational approach called CASGAP - Computational Approach for Structure Generation of Anisotropic Particles - for generating any desired three dimensional real-space structure of anisotropic building blocks (modeled as particles) adhering to target distributions of particle shape, size, and positional and orientational order.


Specificity in lipases: a computational study of transesterification of sucrose.
Computational conformational searches of putative transition states of the reaction of sucrose with vinyl laurate catalyzed by lipases from Candida antarctica B and Thermomyces lanuginosus have been carried out. The dielectric of the media have been varied to understand the role of protein plasticity in modulating the observed regioselective transesterification. The binding pocket of lipase from Candida adapts to the conformational variability of the various substates of the substrates by small, local adjustments within the binding pocket. In contrast, the more constrained pocket of the lipase from Thermomyces adapts by adjusting through concerted global motions between subdomains. This leads to the identification of one large pocket in Candida that accommodates both the sucrose and the lauroyl moieties of the transition state, whereas in Thermomyces the binding pocket is smaller, leading to the localization of the two moieties in two distinct pockets; this partly rationalizes the broader specificity of the former relative to the latter. Mutations have been suggested to exploit the differences towards changing the observed selectivities.


Structure, diversity and expression of the TCRdelta chains in the Mexican axolotl.
Mammals and birds have two major populations of T cells, based on the molecular composition and biological properties of their antigen receptors (TCR). alpha beta T cells recognize antigenic peptides linked to major histocompatibility complex (MHC) molecules, and gamma delta T cells recognize native peptide or non-peptide antigens independently of MHC. Very little is known about gamma delta T cells in ectothermic vertebrates. We have cloned and characterized the TCRdelta chains of an urodele amphibian, the Mexican axolotl (Ambystoma mexicanum). The Cdelta domain is structurally similar to its mammalian homologues and the transmembrane domain is very well conserved. Four of the six Valpha regions that can associate with Calpha (Valpha2, Valpha3, Valpha5 and Valpha6) can also associate with Cdelta, but no specific Vdelta regions were found. This suggests that the axolotl TRD locus is nested within the TRA locus, as in mammals, and that this organization has been present in all tetrapod vertebrates and in the common ancestor of Lissamphibians and mammals, for over 400 million years. Two Jdelta regions were identified, but no Ddelta segments were clearly recognized at the Vdelta-Jdelta junctions. This results in shorter and less variable CDR3 loops than in other vertebrates and the size range of the Vdelta-Jdelta junctions is similar to that of mammalian immunoglobulin light chains. Equivalent quantities of TRD mRNA were found in the lymphoid organs, and in the skin and the intestines of normal and thymectomized axolotls. The analysis of several Valpha/delta6-Cdelta and Vbeta7-Cbeta junctions showed that both the TCRdelta and the TCRbeta chains were limited in diversity in thymectomized axolotls.


Preliminary experience with patch-enlarged brachial artery for hemodialysis access.
The patency of patch-enlarged (capsule-shaped) brachial arteries for long-term hemodialysis access was evaluated retrospectively. Twelve brachial arteries were patched with polytetrafluoroethylene (PTFE) grafts (standard wall thickness), making 1 x 2 cm aneurysms proximal to the elbow joints in 10 patients (six men with six patches, four women with six patches; patient age: 53 to 76 years, mean age +/- SD: 65.4 +/- 8.5 years) between September 2001 and April 2002. Ten patches were needled for each hemodialysis session as blood-drawing ports. The port's 1-year primary patency rate was 90%, 2-year patency was 70%, and 3-year patency was 70%. Two patches were needled in each hemodialysis session for dialyzed blood infusion access; both clotted within 1 year, with intact vessel continuity. Patch enlargement (capsule-shaped) of the brachial artery with a PTFE graft can be used as a long-term blood-drawing access in selected patients. This novel access may help patients with central vein stenosis or occlusion (which some patients had) and may help patients who have comorbid conditions such as chronic congestive heart failure or liver cirrhosis with ascites.


Intracellular localization of pp60c-src in human platelets.
We have studied the intracellular distribution of the proto-oncogene product pp60c-src in human platelets by immunofluorescence microscopy and by immunogold electron microscopy on frozen thin sections. Virtually all of the immunoreactive pp60c-src was found to be associated with the plasma membrane and with membranes of the surface-connected canalicular system. This localization suggests that pp60c-src may relay signals from an as yet unidentified cell surface protein to intracellular targets.


Multiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord.
Quantitative MRI measures of multiexponential T(2) relaxation and magnetization transfer were acquired from six samples of excised and fixed rat spinal cord and compared with quantitative histology. MRI and histology data were analyzed from six white matter tracts, each of which possessed unique microanatomic characteristics (axon diameter and myelin thickness, in particular) but a relatively constant volume fraction of myelin. The results indicated that multiexponential T(2) relaxation characteristics varied substantially with variation of microanatomy, while the magnetization transfer characteristics remained close to constant. The most-often-cited multiexponential T(2) relaxation metric, myelin water fraction, varied by almost a factor of 2 between two regions with myelin volume fractions that differed by only approximately 12%. Based on the quantitative histology, the proposed explanation for this variation was intercompartmental water exchange, which caused the underestimation of myelin water fraction and T(2) values and is, presumably, a greater factor in white matter regions where axons are small and myelin is thin. In contrast to the multiexponential T(2) relaxation observations, magnetization transfer metrics were relatively constant across white matter tracts and concluded to be relatively insensitive to intercompartmental water exchange.


Computer-Assisted In Sensu Exposure for Posttraumatic Stress Disorder: Development and Evaluation.
Dissociative states during psychotherapy sessions reduce the benefit of exposure-based therapy for posttraumatic stress disorder (PTSD). Thus, in evidence-based therapeutic programs such as dialectical behavior therapy for PTSD (DBT-PTSD), therapists apply specific antidissociative skills to reduce dissociative features during in sensu exposure. In addition to therapist-guided sessions, exposure protocols often require that the patients listen to audio recordings of exposure sessions in self-management. The problem of how to prevent dissociative features during such self-administered exposure exercises has not been resolved yet. Hence, we developed the computer program MORPHEUS that supports the application of self-administered exposure exercises. MORPHEUS continuously monitors the level of dissociative states and offers state-related antidissociative skills. This study sought to examine the acceptance and feasibility of the MORPHEUS program. Patients who underwent 12 weeks of residential DBT-PTSD treatment used MORPHEUS during exposure exercises in self-management. After the treatment, they filled out evaluation questionnaires. In sum, 26 patients receiving a 12-week standard DBT-PTSD program participated in this study; 2 participants could not be analyzed because of missing data. All the patients used MORPHEUS as often as it was required according to the DBT-PTSD treatment (2 to 5 times a week). The overall acceptance and feasibility as rated by the patients was high: for example, patients found the skills useful to block dissociation (mean 4.24 on a scale from 0 to 5, SD 0.24) and stated that they would use the program again (mean 4.72 on a scale from 0 to 5, SD 0.11). Furthermore, patients indicated that they would recommend MORPHEUS to a friend (mean 4.44 on a scale from 0 to 5, SD 0.12). In 82% (32/39) of the cases, the use of antidissociative skills was related to a decrease in dissociation. In 18% (5/39), dissociation remained unchanged or increased. The evaluative data suggest high acceptability and feasibility of MORPHEUS. Further studies should evaluate the effectiveness of the skills applied during the program. World Health Organization International Clinical Trials Registry Platform: DRKS00006226; http://apps.who.int/trialsearch/Trial2.aspx?TrialID= DRKS00006226 (Archived by WebCite at http://www.webcitation.org/ 6hxuFbIUr).


Interplay between liquid crystalline and isotropic gels in self-assembled neurofilament networks.
Neurofilaments (NFs) are a major constituent of nerve cell axons that assemble from three subunit proteins of low (NF-L), medium (NF-M), and high (NF-H) molecular weight into a 10 nm diameter rod with radiating sidearms to form a bottle-brush-like structure. Here, we reassemble NFs in vitro from varying weight ratios of the subunit proteins, purified from bovine spinal cord, to form homopolymers of NF-L or filaments composed of NF-L and NF-M (NF-LM), NF-L and NF-H (NF-LH), or all three subunits (NF-LMH). At high protein concentrations, NFs align to form a nematic liquid crystalline gel with a well-defined spacing determined with synchrotron small angle x-ray scattering. Near physiological conditions (86 mM monovalent salt and pH 6.8), NF-LM networks with a high NF-M grafting density favor nematic ordering whereas filaments composed of NF-LH transition to an isotropic gel at low protein concentrations as a function of increasing mole fraction of NF-H subunits. The interfilament distance decreases with NF-M grafting density, opposite the trend seen with NF-LH networks. This suggests a competition between the more attractive NF-M sidearms, forming a compact aligned nematic gel, and the repulsive NF-H sidearms, favoring a more expansive isotropic gel, at 86 mM monovalent salt. These interactions are highly salt dependent and the nematic gel phase is stabilized with increasing monovalent salt.


Medium-chain triglycerides are advantageous in promoting weight loss although not beneficial to exercise performance.
Medium-chain triglycerides (MCT) are triglycerides with a fatty acid chain length varying between 6 and 10 carbon atoms. MCT differ from long-chain triglycerides as they are relatively soluble in water and, hence, rapidly hydrolysed and absorbed. MCT are transported in the blood through the portal system, consequently they bypass adipose tissue that makes them less susceptible to hormone-sensitive lipase and deposition into adipose tissue stores. Due to these properties, MCT have been researched for both benefits to exercise performance and health. The present review aims to assess whether MCT are beneficial in either of these situations. MCT have been proposed as a means to maximizing an athlete's ability to maintain their glycogen stores so they can be more competitive. However, only two studies to date have shown an improvement in exercise performance. From a health perspective, MCT increase fat oxidation and energy expenditure as well as reduce food intake and beneficially alter body composition. Results indicate that MCT feeding is ineffective in improving exercise performance and future work should focus on the health benefits and applications of MCT.


[Diagnostic and treatment of overactive bladder].
The overactive bladder (OAB) is characterized by symptoms of frequency, urgency, nocturia, and urge incontinence, substantially affecting the quality of life of millions of people throughout the world. Diagnosis of OAB made on patient history, physical examination, and clinical tests can be used as the basis for treatment in most cases. In cases where there is uncertainty regarding the diagnosis, urodynamic assessment should be carried out. Treatment of OAB includes behavioral therapy, pharmacology and, in some cases, surgery. This article reviews current findings regarding diagnostics and treatment of the overactive bladder.


Custodiol-N™ cardioplegia lowers cerebral inflammation and activation of hypoxia-inducible factor-1α.
Cardioplegic solutions induce cardiac arrest and protect cardiac tissue from ischaemia-reperfusion injury. However, the effects on the brain, which is vulnerable to cardiopulmonary bypass (CPB) surgery and ischaemia-reperfusion injury, mostly remain unknown. We investigated if cardioplegic solutions differ in their effects in altered oxygen conditions and in their ability to induce cerebral inflammation. Thirty pigs were subjected to a midline sternotomy and CPB at 34°C with 90 min cardiac arrest followed by 120 min reperfusion. Following randomization on a 1:1:1 basis, they received either a single shot of histidine-tryptophan-α-ketoglutarate (HTK)-Bretschneider solution (n = 10), histidine-tryptophan-α-ketoglutarate-N (HTK-N; n = 10) or HTK plus 1.2 mg/l cyclosporine A (HTK/CsA; n = 10). Brain regions of interest (frontal cortex, cerebellum, brain stem, diencephalon, colliculus superior) were analysed by real time quantitative reverse transcriptase polymerase chain reaction for hypoxia-inducible factor-1α (HIF-1α), tumour necrosis factor-α, interleukin (IL)-10, IL-1β and IL-1β receptor as well as by immunohistochemical analysis for HIF-1α. Blood gas and electrolyte analyses were performed. Comparisons between baseline and reperfusion period levels revealed that HTK-N cardioplegia induced a smaller reduction of the haemoglobin content and blood calcium concentrations (hbbaseline: 5.97 ± 0.63 mmol/l; hbreperfusion: 6.16 ± 0.66 mmol/l; P = 0.428; Cabaseline2+: 1.36 ± 0.05 mmol/l; Careperfusion2+: 1.28 ± 0.05 mmol/l; P < 0.001) compared to HTK (hbbaseline: 5.93 ± 0.45 mmol/l; hbreperfusion: 4.72 ± 0.79 mmol/l; P = 0.001; Cabaseline2+: 1.34 ± 0.07 mmol/l; Careperfusion2+: 1.24 ± 0.06 mmol/l; P = 0.004) and HTK/CsA cardioplegia (hbbaseline: 5.88 ± 0.44 mmol/l; hbreperfusion: 5.14 ± 0.87 mmol/l; P = 0.040; Cabaseline2+: 1.38 ± 0.04 mmol/l; Careperfusion2+: 1.20 ± 0.14 mmol/l; P = 0.001). Brain region-specific regulation of the HIF-1α expression, no general HIF-1α activation and a lower tumour necrosis factor-α expression (pto HTK = 0.050, pto HTK/CsA = 0.013) were documented for HTK-N cardioplegia. HTK-N (Custodiol-N) induced fewer cerebral effects and less inflammation during CPB surgery than HTK and HTK/CsA cardioplegia. These data suggest that HTK-N exerts brain protective effects during and after CPB surgery.


[Circumventing multidrug resistance in human cancer by anti-ribozyme].
The demonstration tha RNA can be cleavaged by cis-ribozyme(catalytic RNAs, RNA enzyme) has potentially important therapeutic implications. Ribozymes are effective for modulation of gene expression because of their simple structure, site-specific cleavage activity and catalytic potential. The targets of ribozyme-mediated gene modulation have ranged from cancer cells to foreign genes that cause infectious diseases. Additional target sites for ribozymes are in initial phases of development and design. Ribozymes have been targeted against myriad genes, including oncogenes (ras, BCR-ABL) and drug resistance genes(MDR-1, c-fos, DHFR). These ribozymes have cleaved the target RNAs in culture system(in vitro) and developed in vivo system. We reported that anti-fos ribozyme has altered the expression of c-fos and DNA repair genes in cisplatin-resistance cancer cells, and reversed the sensitivity to ciaplatin. Furthermore, we have developed high efficiency by the transfer system using an electroporation in vivo.